The objective of this proposal is to utilize in vivo immunizations and in vitro lymphocyte culture techniques to discern the B-cell defects in immune deficient patients. We have shown that after immunization, individual patients have a variable capacity to generate specific B-lymphocyte subpopulations characterized in normal individuals by temporal appearance in the circulation, size, isotype of antibody produced and surface marker phenotypes. Additionally, we have developed in vivo and in vitro model systems for B-cell tolerance which appear to mimic the B-cell defects seen in many immune deficient patients. Future studies will continue the structural and functional analyses of the b-cell subsets in immune deficient patients and determine the role of B-cell tolerance in the pathogenesis of their diseases.